Gut, Microbiome, and Brain Regulatory Axis: Relevance to Neurodegenerative and Psychiatric Disorders

Abstract

It has become apparent that the molecular and biochemical integrity of interactive families, genera, and species of human gut microflora is critically linked to maintaining complex metabolic and behavioral processes mediated by peripheral organ systems and central nervous system neuronal groupings. Relatively recent studies have established intrinsic ratios of enterotypes contained within the human microbiome across demographic subpopulations and have empirically linked significant alterations in the expression of bacterial enterotypes with the initiation and persistence of several major metabolic and psychiatric disorders. Accordingly, the goal of our review is to highlight potential thematic/functional linkages of pathophysiological alterations in gut microbiota and bidirectional gut–brain signaling pathways with special emphasis on the potential roles of gut dysbiosis on the pathophysiology of psychiatric illnesses. We provide critical discussion of putative thematic linkages of Parkinson’s disease (PD) data sets to similar pathophysiological events as potential causative factors in the development and persistence of diverse psychiatric illnesses. Finally, we include a concise review of preclinical paradigms that involve immunologically–induced GI deficits and dysbiosis of maternal microflora that are functionally linked to impaired neurodevelopmental processes leading to affective behavioral syndromes in the offspring.

Chromosomal Processes in Mind-Body Medicine: Chronic Stress, Cell Aging, and Telomere Length

“…With regard to microbiome regulation as part of these processes, it has become apparent that the molecular and biochemical integrity of interactive families, genera, and species of human gut microflora is critically linked to maintaining complex mitochondrial, metabolic, and behavioral processes mediated by peripheral organ systems and central nervous system neuronal groupings [ 49 ]. In shaping human gut microbiota, environment dominates host genetics [ 52 ].…”

“… Brain-Gut Coupling and Insular-Vagal Integration. It has become apparent that the molecular and biochemical integrity of interactive families, genera, and species of human gut microflora is critically linked to maintaining complex metabolic and behavioral processes mediated by peripheral organ systems and central nervous system neuronal groupings [ 49 ]. In addition, the vagus nerve may be the primary route through which gut signaling and pathological triggers such as alpha-synuclein travel from the intestines to the brain.…”

“…Here, limbic autoregulation would integrate afferent peripheral inputs with central interoception, insular cortex activity, and emotion/emotional contexts. Accordingly, with mental training and MBI, i.e., cognitively induced health behaviors, the brain (via its motivation and reward circuitries, imbedded in the limbic system) may downregulate upstream (hyper-) activating processes [ 2 , 32 , 42 , 49 – 51 ].…”

Diet, Microbiota and Brain Health: Unraveling the Network Intersecting Metabolism and Neurodegeneration

“…Neurotransmitters produced by GM also exert other functions outside of the nervous system with indirect effects of neuronal function. For instance, serotonin and dopamine affect immune system response [ 38 , 39 ], while GABA plays a role in the local defense against bacterial translocation [ 40 ]. The gut releases significant amounts of hormones, peptides and microbial metabolites, such as short chain fatty acids (SCFAs), secondary bile acids, tryptophan- and polyphenol-derived products, which exerts important effects on neuronal function and survival.…”

Mathematical Biology Models of Parkinson's Disease

“…The aim of Kuznetsov and coworkers was to study PD pathogenesis. Thus, despite being the only work to consider Asyn transport, the authors have not explored the potential of their models to simulate pathology propagation according to the Braak hypothesis.…”